Clay Nanotube Drug Carrier with Enhanced Membrane/Skin Permeability

Halloysite nanoclay is a natural material which is interesting for biomedical applications. Its unique physiochemical structure that forms the tubular shape originates from rolled sheets of aluminosilicate 15-20 times, such that alumina is inside and silica on the outside of the nanotubes, thus defining inner positive and outer negative charges. The dimensions of these tubules vary from 500-1,000 nm in length, external diameter 50-60nm, and inner lumen 12-15nm. Halloysites are biocompatible, cheap, and available in large quantities which suggests that these tubules can be used as effective nanocarriers. In this work, we exploited halloysite as a “nano-torpedo” for targeted drug delivery through the membranes in two ways. We discovered new “larger” nanotubes of 80 nm diameter and 1.6 μm length and used them for skin protection with in depth halloysite drug delivery. In the second part of the work, the use of traditional “smaller” halloysite as a carrier for drug delivery through the blood-brain barrier was developed, both in vitro and in vivo. In this work, we made all drug nanoformulations, and collaborate with Dr. DeCoster lab and Dr. Murray lab in cell and mice experiments. We invented “new” larger halloysite nanotubes and utilized their potential for skin care applications. Analyzing the structure of the halloysite nanotubes provided by NorthStar LLC., we found an increase in dimensions when compared to traditional halloysite. The larger tubes have a length of 1.6 μm and a diameter of 80 nm. Visualization of halloysite dispersibility in water was possible with these larger tubules confirming favorable aqueous dispersibility and structural organization are comparable traditional smaller halloysite. We suggested that the larger tubes formation mechanism could be similar to smaller halloysite (rolling), but initial aluminosilicate sheets were of larger area, thus forming larger tubes. We theorized that these “new” nanotubes would be more efficient in penetration though strong barriers, like skin, for drug delivery due to their size and increased drug loading capacity. Encapsulating vitamin B-12, a known skin protecting agent inside these nanotubes create a new formulation with sustained B-12 release when admixed to traditional oil-based skin cream. Pig skin was used for initial testing and analysis due to it consisting of a similar epidermis to human skin. Initial results were promising with massaging of such a formulation on skin which provides perpendicular penetration of the halloysite nanotubes. Additionally, we found that for penetration though cell membranes around the brain, smaller halloysite formulations could be more effective. Current treatments for brain disorders such as epilepsy are not effective due to the selectivity of the blood-brain barrier (BBB) preventing drug delivery. Utilizing traditional small halloysite with dimensions of 500-800 nm in length and external diameter of 50-60 nm and inner lumen 12-15 nm, we conducted in vitro experiments of halloysite formulations as a “nano-torpedo” penetrating brain microvascular endothelial cell (BMVECs). Through fluorescent and real time calcium imaging techniques we proved a prolonged gradual drug delivery mechanism by the encapsulation of rhodamine isothiocyanate and ionomycin within the nanotube. With delayed diffusion, the nanotubes effectively delivered the drug to the primary BMVECs without causing any toxic effects or killing them, by binding and penetration in time periods of 1 to 24 h. Furthermore, constructing a two layer (astrocytes and endothelial) synthetic blood-brain model barrier with a 0.4 um porous transwell support enabling us to study structures closer to the BBB. The confluence of the bilayer of astrocyte and endothelial cells was examined using a non-inverted microscope after Diff-Quik staining of the cells. The halloysite rhodamine formulations were tested on this barrier by treating the samples to the dual layer of endothelial / astrocyte cells and allowing them to pass through the barrier on their own. Proving its penetration by measuring the fluorescence at the bottom of the membrane after 24 h. The fluorescence signal grew moderately in the first hour but by 24 h it had increased to 85 %. In the last section of this work, in vivo experiments on halloysite delivery to the brains of mice via intranasal administration were conducted in collaboration with Y. Yanamadala. Halloysite formulations with encapsulation of rhodamine isothiocyanate to track halloysite as it moves throughout the brain were developed. We produced the nanoclay loading of diazepam and xylazine which are two commonly used drugs for their anxiolytic and sedation effects. Wild type C57BL/6NHsd were purchased from Jackson Laboratory and these three halloysite formulations were intranasally delivered to mice. Analysis of the olfactory bulb and cortex were accomplished through multiple microscopy techniques and the overall condition of the mice were measured by behavioral studies such as rotarod, novel object recognition, and open field tests over the course of seven days. In this collaborative work we proved not only delivery of halloysite to the brain by passing the blood-brain barrier, but also have shown that its presence in the brain was not harmful to the behavior or well-being of the mice. Therefore, potentially, such halloysite-drug delivery may be used for urgent brain disease treatment with deposition / of this biocompatible nanoclay residues

TOWARDS FACING GLOBAL FAMINE: MODELING FOOD DISTRIBUTION ACCORDING TO IRAQI CASE

The total population facing malnutrition and hunger is about one billion at the global level. As the global population increases from 7.3 billion in 2015 to 9.2 billion in 2050, the total new population that needs to be fed until 2050 is 2 billion. This was in addition to the one billion people facing starvation. Additional food products should be combined together to feed an additional population of three billions in thirty five years to come. Due to the constraint of agricultural land and food production deficit to meet the food security standard of a population of more than nine billion, global famine is expected to prevail unless hard work is done at both the national and the international scales in two dimensions under the help of the United Nations (FAO, WFP, and UNICAFE). The first dimension is increasing total food output to meet the need of all the people for a healthy and active food requirements. In the second dimension which is due to the wide discrepancies of income distribution between countries and within countries, it is necessary to adopt subsidized food distribution system at the national scale for countries where their population largely or partially cannot afford to obtain the required food at all time. The core of this paper is the second dimension with reference to Iraqi food distribution system adopted during thirteen years of comprehensive sanction, and it was proven to be successful in saving Iraqi people from famine. It was mentioned that the public food distribution which was recently adopted in India covers 800 million persons. This paper proposed guidelines for building infrastructure like silos and large warehouses for strategic reserve to secure the flow of food. This has to be facilitated by preparing transport network to carry food from ports or local farmers to silos and warehouses, and to deliver food through network of private retailers so that beneficiaries can obtain food from their residential areas. National aid is required for counties facing malnutrition and starvation

A Study OF the Electronic Structure of Azabenzen Molecules: by B3LYP-DFT Density Functional Calculation

In this work, five molecules are optimized at B3LYP/6-31G** density functional theory. Benzene molecule was a reference. Electronic properties of azabenzene molecules were investigated depending on the three parameters (B3LYP) density functional theory. The best geometry for all molecules were investigated using (6-31G**) basis sets. The total energies, energy gaps, ionization potentials, electron affinities by use adiabatic and koopman methods . Adding CN cluster atoms  in different position for the less Eg (pyridazine)molecular leads to decrease the energy gap in the second position comparison with the pyridazine molecular

Bioactive Glasses in Dental Applications (Literature Review)

يكون الزجاج الحيوي من اساس سيليكات يمكنها ترتيب ارتباط كيميائي القوي مع الأنسجة. هذه المواد الحيوية متوافقة حيويا للغاية ويمكن أن تشكل طبقة هيدروكسيباتيت عند زرعها في الجسم أو مغمورة في سائل الجسم المشبع. نظرًا للعديد من العيوب يتم استبدال طريقة معالجة الزجاج التقليدية بما في ذلك ذوبان مكونات الزجاج بطريقة سول-جيل مع عدد كبير من الفوائد مثل درجة حرارة المعالجة المنخفضة، نقاء عالي والتجانس وبالتالي تحكم أفضل في النشاط الحيوي. يحتوي الزجاج النشط بيولوجيًا على مجموعة واسعة من التطبيقات، خاصةً في طب الأسنان. يمكن استخدامه كجسيمات أو أشكال متجانسة وبنيات مسامية أو كثيفة في تطبيقات مختلفة مثل إعادة التمعدن أو معالجة فرط الحساسية. يمكن الترويج لبعض خصائص الزجاج الحيوي النشطة بيولوجيا مثل خصائص مضادة للجراثيم عن طريق إضافة عناصر مختلفة في الزجاج. يمكن استخدامه بيولوجيًا لتعديل المواد المختلفة الحيوية التي تحتاج إلى أن تكون نشطة بيولوجيًا. تستعرض هذه الدراسة التطورات الهامة للزجاج الحيوي في طب الأسنان. علاوة على ذلك، سنناقش مجالات تطور الزجاج من البداية إلى التطورات الجارية، والتي تشمل طرق المعالجة والتطبيقات وخصائص هذه النظارات. Bioactive glasses are silicate-grounded and can course of action a strong substance connect through the tissues. These biomaterials are exceptionally biocompatible and can shape a hydroxyapatite layer when embedded in the body or absorbed the recreated body liquid. Because of a few detriments, regular glass preparing technique, including softening of glass parts is supplanted by sol-gel strategy with a substantial number of advantages, for example, low handling temperature, higher immaculateness and homogeneity and along these lines better control of bioactivity. Bioactive glasses have a wide scope of utilizations, especially in dentistry. These glasses can be utilized as particulates or solid shapes and permeable or thick develops in various applications, for example, remineralization or extreme touchiness treatment. A few properties of bioactive glasses, for example, antibacterial properties can be advanced by including diverse components into the glass. Bioactive glasses can likewise be utilized to adjust diverse biocompatible materials that should be bioactive. This investigation surveys the critical advancements of bioactive glasses in dentistry. Besides, we will examine the field of bioactive glasses from starting to the present advancements, which incorporates preparing techniques, applications, and properties of these glasses

Determination of significant parameters that drive fracture optimization in the Glauconite Formation, Southern Chile

The Glauconite Formation in the Magallanes Basin of Southern Chile is a clay- and silica-rich formation with low permeability. As with many of the unconventional resources, the Glauconite Formation requires a hydraulic fracturing operation to enhance the productivity of the wells in this area. Data and pertinent information of fracturing, completion, and reservoir quality parameters along with post-fracture production data were collected to initiate a database of nearly 70 wells, to be used to develop a better understanding of the fracturing behavior, optimize the well stimulation, and overcome the major barriers in the hydraulic fracturing of the Glauconite Formation. The database of Glauconite wells was used in this study to identify the key parameters of the fracturing design, completion, and reservoir quality that have the greatest influence on well performance in this unconventional reservoir. This study also attempts to identify the best treatment fluid to maximize well performance and the effects of different values of the major fracture treatments and completion parameters. Statistical and sensitivity analyses were applied to identify the most effective parameters on the initial production, early recovery, and Estimated Ultimate Recovery. Results of this work show that water fracs are superior to hybrid fracturing fluids. Total fluid and proppant volumes strongly affect well performance. Other completion and reservoir parameters were found to have a lesser impact on well performance in the Glauconite wells of Southern Chile --Abstract, page iii

Comparison of the traditional exponential weighted moving average chart (EWMA) and modified EWMA chart (MEWMA)

Any production process that needs statistical control to exit the production process as required, whether from the consumer or producer point of view, and in this research a comparison was made between the two control charts of the modified and traditional exponential weighted moving average chart. The modified chart takes into consideration the autocorrelation that arises between the observations, unlike the traditional chart, which is affected by the autocorrelation between the values of the observations, which leads to giving inaccurate results on the progress of the production process. To clarify the work of the modified chart and compare it with the traditional chart, data representing the temperature of a chemical industrial process was relied on, because such data are autocorrelation, meaning that small or sudden transformations may occur. The two charts were also applied to data taken from the Quality Control Department in the General Facility for Vegetable Oils in Baghdad Governorate affiliated to the Ministry of Industry. The modified chart showed its efficiency and accuracy in detecting deviations in the production process better than the traditional chart

Behavior of Steel–Lightweight Self Compacting Concrete Composite Beams with Various Degrees of Shear Interaction

This study investigated the use of lightweight self-compacting concrete (LWSCC), which represents a trend in producing high-performance concrete, as slabs in steel-concrete composite beams with headed studs as shear connectors. Three push-out test specimens were fabricated and tested to assess the shear strength and behavior of M16-headed stud connectors embedded in LWSCC. Based on the push-out test results, six steel-LWSCC composite beams were manufactured and tested as simply supported composite beams. In addition, a steel-normal weight self-compacting concrete (NWSCC) composite beam specimen with full shear interaction was manufactured and tested for comparison. The main variables taken into account in this study were the degree of shear interaction and regions of bending moment (sagging or hogging). It was observed that the increase in degree of shear interaction from 50 to 100% improved the ultimate carrying capacity, the service load, and the stiffness of the tested steel-LWSCC beam specimens by a ratio reached to 96, 95, and 122%, respectively, when subjected to sagging bending moments and by a ratio reached to 57, 59, and 134%, respectively, when subjected to hogging bending moments. In addition, it was noted that the deflection and the end slip values for steel-LWSCC specimens under a sagging bending moment are smaller than those under a hogging bending moment, which have the same degree of shear interaction and at the same load level. Moreover, the experimental results show that the ultimate carrying capacity, service load, and stiffness values for the steel-NWSCC composite beam were higher than those for the steel-LWSCC beam specimens that have the same properties, while the ultimate deflection and end slip were smaller. Doi: 10.28991/CEJ-2023-09-11-04 Full Text: PD